Journal of Andrology
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Published-Ahead-of-Print January 22, 2009, DOI:10.2164/jandrol.108.005843

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Length of Androgen Receptor-CAG Repeats in Fertile and Infertile Egyptian Men

Wael A. Badran , Ibrahim Fahmy , Wael M. Abdel-Megid , Kay Elder , Ragaa Mansour , and Marijo Kent-First *

* To whom correspondence should be addressed. E-mail: mk247{at}msstate.edu.

Androgens play key roles in spermatogenesis, and exert their effect via the androgen receptor (AR). The AR gene has a repetitive DNA sequence in exon 1 that encodes a polyglutamine tract. Instability in the glutamine (CAG) repeat unit length is polymorphic across ethnic groups. Previous studies of the relationship between the repeat unit length and male infertility have been contradictory. To establish the range of wild type alleles in Egyptian males, we determined the range of repeat lengths in a population of normally fertile ethnically selected Egyptian males. We also investigated the association between trinucleotide repeat length within the AR gene and male factor infertility in a population of ethnically selected Egyptian infertile males which were compared with fertile, ethnic group and age matched controls. The study included 129 clinically selected infertile Egyptian men that were scheduled for ICSI and 52 ethnically matched fertile controls. The experimental population was grouped according to sperm counts ranging from non obstructive azoospermia to normozoospermia. The CAG repeat N-terminal domain region of the AR gene was amplified in peripheral blood DNA and allele size was determined by fragment analysis. Allele size and single Nucleotide Polymorphism (SNP) and mutation rate were determined by sequencing individual amplified alleles. The mean CAG repeat length in the azoospermia group was 18.55 ± 2.0, in the severe oligozoospermia group was 18.21 ± 3.42, in the oligozoospermia group 18.27 ± 2.93, and in the infertile with normal sperm count group 17.72 ± 2.0. In the control group the mean CAG repeat length was 18.18 ± 3.63. No significant correlation was found between CAG repeat length and the risk of male factor infertility in an ethnically defined population of Egyptian males. However a significant and positive correlation between CAG repeat length and serum testosterone concentration was demonstrated, which suggests the involvement of epigenetic regulation linked to this region.


Key words: Androgen • Assisted reproduction • ICSI • Infertility • Spermatogenesis • Androgen receptor • CAG repeats • male inferility • trinucleotide repeat






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